Acute kidney injury (AKI) is common, expensive to treat, and is associated with >50% mortality despite advances in supportive care. Each year, millions of patients undergo cardiovascular surgery, medical imaging procedures, or cytotoxic chemotherapy, placing them at significant risk for developing AKI. However, while there is an immense clinical need to identify patients at high risk for developing AKI, predictive models do not currently exist. To make matters worse, there are no pharmacologic therapies available for the prevention or treatment of AKI, despite a $6.3 billion market opportunity in the US. A principal reason for the lack of therapies is the lack of biomarkers capable of identifying patient at high risk for AKI that can be used as an enrichment strategy to power phase 2/3 clinical trials. HealthSpan Dx has identified a biomarker that has potential to predict patients at risk for AKI. Our findings in a human clinical trial point to a marker of senescence, p16INK4a as predictor of risk of AKI in patients undergoing cardiovascular procedures. Senescent cells lack replicative capacity and, therefore, cannot contribute to tissue repair and homeostasis. In kidney, where normally quiescent epithelial cells need to rapidly proliferate to recover from ischemic shock, accumulation of senescent cells hinders regeneration and leads to kidney injury. A test to measure expression of p16INK4a mRNA in peripheral blood has been developed in the Sharpless lab and evaluated in various clinical scenarios in >1,000 human patients. IP around this marker was issued in 2012 and is the core technology of HealthSpan Dx. HealthSpan Dx is developing the assay for commercialization and is actively exploring areas of clinical need. In this proposal, we will perform proof-of-concept experiments to determine the utility of p16INK4a assay for prediction of AKI after cardiac bypass surgery. Completion of this Phase I proposal will provide the requisite data to seek Phase II funding for multi-center clinical trials to further validate clinical utility of the p16INK4a diagnostic as a predictor of AKI in patients undergoing cardiovascular procedures. Ultimately, validation of the p16INK4a diagnostic as a predictor of AKI would catalyze the clinical development of novel preventative and treatment approaches for AKI.